目的选择阳离子交换介质Streamline SP分离纯化anti-HBsAg Fab的最适吸附条件。方法试管法分别测定平衡缓冲液在不同pH和不同离子强度下,阳离子交换介质Streamline SP对预分离纯化蛋白的吸附效果。用1 ml SP预装柱及自装28 ml Streamlin...目的选择阳离子交换介质Streamline SP分离纯化anti-HBsAg Fab的最适吸附条件。方法试管法分别测定平衡缓冲液在不同pH和不同离子强度下,阳离子交换介质Streamline SP对预分离纯化蛋白的吸附效果。用1 ml SP预装柱及自装28 ml Streamline SP柱进行离子交换层析以验证吸附效果。结果 NaAc-HAc作为平衡缓冲液在pH4．4、离子强度100～600mmol／L可以使阳离子交换介质Streamline SP与蛋白吸附达到最佳效果。在该条件下用1 ml SP预装柱及自装28 ml SP柱进行离子交换层析,均验证了这一吸附效果。结论试管法选择的离子交换层析的最适吸附条件用于从大肠杆菌中初步分离纯化anti-HbsAg Fab切实可行。展开更多
AIM:To evaluate the incidence and risk factors of Korean tuberculosis(TB) infection in patients with inflammatory bowel disease(IBD) undergoing anti-TNF treatment.METHODS:The data of IBD patients treated with anti-TNF...AIM:To evaluate the incidence and risk factors of Korean tuberculosis(TB) infection in patients with inflammatory bowel disease(IBD) undergoing anti-TNF treatment.METHODS:The data of IBD patients treated with anti-TNFs in 13 tertiary referral hospitals located in the southeastern region of Korea were collected retrospectively.They failed to show response or were intolerant to conventional treatments,including steroids or immunomodulators.Screening measures for latent TB infection(LTBI)and the incidence and risk factors ofactive TB infection after treatment with anti-TNFs were identified.RESULTS:Overall,376 IBD patients treated with antiTNF agents were recruited(male 255,mean age of anti-TNF therapy 32.5±13.0 years);277 had Crohn’s disease,99 had ulcerative colitis,294 used infliximab,and 82 used adalimumab.Before anti-TNF treatment,screening tests for LTBI including an interferon gamma release assay or a tuberculin skin test were performed in 82.2%of patients.Thirty patients(8%)had LTBI.Sixteen cases of active TB infection including one TB-related mortality occurred during 801 personyears(PY)follow-up(1997.4 cases per 100000 PY)after anti-TNF treatment.LTBI(OR=5.76,95%CI:1.57-21.20,P=0.008)and WBC count<5000 mm3(OR=4.5,95%CI:1.51-13.44,P=0.007)during follow-up were identified as independently associated risk factors.CONCLUSION:Anti-TNFs significantly increase the risk of TB infection in Korean patients with IBD.The considerable burden of TB and marked immunosuppression might be attributed to this risk.展开更多
AIM To investigate the correlation between rs2910164, rs11 614913, rs113054794, and rs188519172 polymorphisms and response to anti-TNF treatment in patients with Crohn's disease(CD). METHODS One hundred seven pati...AIM To investigate the correlation between rs2910164, rs11 614913, rs113054794, and rs188519172 polymorphisms and response to anti-TNF treatment in patients with Crohn's disease(CD). METHODS One hundred seven patients with CD based on standardclinical, endoscopic, radiological, and pathological criteria were included in the study. They all received infliximab or adalimumab intravenously or subcutaneously at standard induction doses as per international guidelines. Clinical and biochemical response was assessed using the HarveyBradshaw index and CRP levels respectively. Endoscopic response was evaluated by ileocolonoscopy at week 12-20 of therapy. The changes in endoscopic appearance compared to baseline were classified into four categories, and patients were classified as responders and nonresponders. Whole peripheral blood was extracted and genotyping was performed by PCR.RESULTS One hundred and seven patients were included in the study. Seventy two(67.3%) patients were classified as complete responders, 22(20.5%) as partial while 13(12.1%) were primary non-responders. No correlation was detected between response to anti-TNF agents and patients' characteristics such as gender, age and disease duration while clinical and biochemical indexes used were associated with endoscopic response. Concerning prevalence of rs2910164, rs11614913, and rs188519172 polymorphisms of miR-146, miR-196a and miR-224 respectively no statistically important difference was found between complete, partial, and non-responders to antiTNF treatment. Actually CC genotype of rs2910164 was not detected in any patient. Regarding rs113054794 of miR-221, normal CC genotype was the only one detected in all studied patients, suggesting this polymorphism is highly rare in the studied population.CONCLUSION No correlation is detected between studied polymorphisms and patients' response to anti-TNF treatment. Polymorphism rs113054794 is not detected in our population.展开更多
Objective: To evaluate the effect of anti-TNF therapy on resistance to insulin in patients with rheumatoid arthritis (RA) compared with patients with RA being treated with non-biological DMARDs. Methods: Inactive pati...Objective: To evaluate the effect of anti-TNF therapy on resistance to insulin in patients with rheumatoid arthritis (RA) compared with patients with RA being treated with non-biological DMARDs. Methods: Inactive patients diagnosed with RA (ACR 1987 criteria) (DAS 28 2.6) were included, being treated with anti-tumor necrosis factor inhibitors (anti-TNF) (cases) and non-biological disease-modifying anti-rheumatic drugs (DMARD) (controls), without risk factors for insulin resistance (administration of steroids, body mass index > 25 kg/m2, diabetes mellitus or use of glucose lowering agents, systemic arterial hypertension or use of anti-hypertensive drugs, triglycerides > 150 mg/dl, hypercholesterolemia > 200 mg/dl, high-density lipoproteins 40 mg/dl in men and 50 mg/in women, or with lipids lowering agents, waist measurement > 88 cm in women and > 102 cm in men). We used HOMA (Homeostasis Model Assessment) to determine insulin resistance in both groups, HOMA being defined as >1 and sensitivity to insulin using QUICKI (Insulin Sensitivity Check Index), ≥0.38 being considered as normal. The Mann Whitney U was used for the statistical analysis. Results: A total of 28 patients, 15 being treated with non-biological DMARDs and 13 with anti-TNF therapy, were evaluated;89.7%, of which were women. Average age: 43.5 (range 21 - 62);the average HOMA index of the non-biological DMARD group was 1.58 (range 0.7 - 5.4), compared with patients treated with anti-TNF therapy, 1.18 (range 0.2 - 4.3) (P = 0.5). The average QUICKI index was 0.36 (range 0.30 - 0.42) in patients treated with non-biological DMARD, compared with0.37 inpatients treated with anti-TNF therapy (range 0.30 - 0.51) (P = 0.8). Conclusion: Resistance to insulin manifested itself in both groups, although there was a greater trend of less insulin resistance and greater sensitivity in the anti-TNF group;this was probably not statistically significant due to the sample size.展开更多
Summary： The anti-tumor effect and mechanism of SEA-Fab＇ coupled protein on gastric tumor was studied. The target cell Walke-256 was treated with SEA-Fab＇ synthesized chemically or SEA respectively for 24 h, 36 h o...Summary： The anti-tumor effect and mechanism of SEA-Fab＇ coupled protein on gastric tumor was studied. The target cell Walke-256 was treated with SEA-Fab＇ synthesized chemically or SEA respectively for 24 h, 36 h or 72 h. PBMC＋Walke-256 cells served as controls. The apoptotic index of SEA-Fab＇ against effector cells was detected. In the mouse gastric cancer models （n=60）, SEA-Fab＇, SEA and normal saline was injected in experimental group, SEA group and control group respectively. The occurrence and weight of tumor was observed. The results showed that the apoptotic index was significantly higher in the SEA-Fab＇ （34.6 -68.9%） and SEA group （15.5-31.9%） than in PBMC＋Walker-256 group （5.5%-12.8%） with the difference being significant （P〈0.01）. And there was significant difference between SEA-Fab＇ group and SEA group （P〈0.01）. The tumor weight in SEA-Fab＇, SEA and control groups was 3.6±0.53 g, 0. 78±0. 26 g and 0.49±0. 17 g respectively with the difference being statistically significant between the SEA-Fab＇ group, SEA group and the control group （P〈0.01）. In the SEA-Fab＇s and SEA groups, there were CD4^＋ T and CD8^＋ T cell infiltrates, but in the cotnrol group, no or few T lymphocytes were seen in the mouse tumor tissue. It was concluded that SEA-Fab＇ was more effective to activate T lymphocytes to kill the tumor cells than SEA used alone. It was feasibility by using the monoclonal antibody as carrier to perform the targeted Immunotherapy of gatric tumor.展开更多
In 1974, in Nature, one of us has proposed a radically new idea that led to the development of anticytokine therapy which is now used around the world for the treatment of autoimmune diseases. We were the first to use...In 1974, in Nature, one of us has proposed a radically new idea that led to the development of anticytokine therapy which is now used around the world for the treatment of autoimmune diseases. We were the first to use antibodies to IFN-γ and were some of the first to suggest using antagonists of TNF-α in the treatment of autoimmune and inflammatory diseases as well. Our method suppresses one of the main pathogenetic mechanisms of these diseases. Antibodies to IFN-γ and TNF-α exhibit dramatic effects on clinical manifestations of rheumatoid arthritis (RA). However, in our trial ultrasound assessment of the synovial membrane thickness in RA patients showed that only anti-IFN-γ exerted pronounced anti-inflammatory effect. Some patients who underwent treatment with antibodies to TNF-α developed a number of complications. Anticytokine therapy (mono- and poly-) alone or in combination with other drugs can possibly be used not only in the treatment of autoimmune diseases, but also in other pathologies with cytokine synthesis disturbances (a number of neurological, psychiatric, endocrine, and other diseases).展开更多
The increase risk of cancer development in patients with inflammatory intestinal disease (IBD) has already studied for decades. The anti-TNF therapy has changed the treatment strategy of IBD. By using on a larger scal...The increase risk of cancer development in patients with inflammatory intestinal disease (IBD) has already studied for decades. The anti-TNF therapy has changed the treatment strategy of IBD. By using on a larger scale and for a longer time, the anti-TNF raised concern over its potential adverse events. A male Crohn’s disease (CD) patient, 55 years old, diagnosed for nine years, treated with infliximab for 6 years. In 2011, he underwent a nupper endoscopy (UE) which showed flat erosive gastritis with moderate intensity in antrum, gastric polyps and gastric erosion. Pathological examination revealed a chronic gastritis in erosive activity and search for Helicobacter pylori resulted positive. In May 2014, the patient was asymptomatic, when it held UE, which showed suggestive lesion of early gastric cancer, measuring 1.5 cm and search for Helicobacter pylori negative. Histopathological exams confirmed the adenocarcinoma. The patient underwent to a laparoscopic surgery (total gastrectomy with lymphadenectomy and reconstruction Roux-en-Y). Risk factors for the development of gastric cancer in general population are already well defined. However studying a possible association among CD and the different therapeutic modalities used in the treatment of this disease with gastric cancer appearance is important to set specific assessment strategies, prevention and follow-up. While there is no consensus on a proper monitoring for gastric cancer prevention in these patients, individualized conduct, taking into account individual characteristics, family record and other risk factors, should be adopted to avoid unfavorable outcomes in CD patients.展开更多
文摘目的选择阳离子交换介质Streamline SP分离纯化anti-HBsAg Fab的最适吸附条件。方法试管法分别测定平衡缓冲液在不同pH和不同离子强度下,阳离子交换介质Streamline SP对预分离纯化蛋白的吸附效果。用1 ml SP预装柱及自装28 ml Streamline SP柱进行离子交换层析以验证吸附效果。结果 NaAc-HAc作为平衡缓冲液在pH4．4、离子强度100～600mmol／L可以使阳离子交换介质Streamline SP与蛋白吸附达到最佳效果。在该条件下用1 ml SP预装柱及自装28 ml SP柱进行离子交换层析,均验证了这一吸附效果。结论试管法选择的离子交换层析的最适吸附条件用于从大肠杆菌中初步分离纯化anti-HbsAg Fab切实可行。
文摘AIM:To evaluate the incidence and risk factors of Korean tuberculosis(TB) infection in patients with inflammatory bowel disease(IBD) undergoing anti-TNF treatment.METHODS:The data of IBD patients treated with anti-TNFs in 13 tertiary referral hospitals located in the southeastern region of Korea were collected retrospectively.They failed to show response or were intolerant to conventional treatments,including steroids or immunomodulators.Screening measures for latent TB infection(LTBI)and the incidence and risk factors ofactive TB infection after treatment with anti-TNFs were identified.RESULTS:Overall,376 IBD patients treated with antiTNF agents were recruited(male 255,mean age of anti-TNF therapy 32.5±13.0 years);277 had Crohn’s disease,99 had ulcerative colitis,294 used infliximab,and 82 used adalimumab.Before anti-TNF treatment,screening tests for LTBI including an interferon gamma release assay or a tuberculin skin test were performed in 82.2%of patients.Thirty patients(8%)had LTBI.Sixteen cases of active TB infection including one TB-related mortality occurred during 801 personyears(PY)follow-up(1997.4 cases per 100000 PY)after anti-TNF treatment.LTBI(OR=5.76,95%CI:1.57-21.20,P=0.008)and WBC count<5000 mm3(OR=4.5,95%CI:1.51-13.44,P=0.007)during follow-up were identified as independently associated risk factors.CONCLUSION:Anti-TNFs significantly increase the risk of TB infection in Korean patients with IBD.The considerable burden of TB and marked immunosuppression might be attributed to this risk.
文摘AIM To investigate the correlation between rs2910164, rs11 614913, rs113054794, and rs188519172 polymorphisms and response to anti-TNF treatment in patients with Crohn's disease(CD). METHODS One hundred seven patients with CD based on standardclinical, endoscopic, radiological, and pathological criteria were included in the study. They all received infliximab or adalimumab intravenously or subcutaneously at standard induction doses as per international guidelines. Clinical and biochemical response was assessed using the HarveyBradshaw index and CRP levels respectively. Endoscopic response was evaluated by ileocolonoscopy at week 12-20 of therapy. The changes in endoscopic appearance compared to baseline were classified into four categories, and patients were classified as responders and nonresponders. Whole peripheral blood was extracted and genotyping was performed by PCR.RESULTS One hundred and seven patients were included in the study. Seventy two(67.3%) patients were classified as complete responders, 22(20.5%) as partial while 13(12.1%) were primary non-responders. No correlation was detected between response to anti-TNF agents and patients' characteristics such as gender, age and disease duration while clinical and biochemical indexes used were associated with endoscopic response. Concerning prevalence of rs2910164, rs11614913, and rs188519172 polymorphisms of miR-146, miR-196a and miR-224 respectively no statistically important difference was found between complete, partial, and non-responders to antiTNF treatment. Actually CC genotype of rs2910164 was not detected in any patient. Regarding rs113054794 of miR-221, normal CC genotype was the only one detected in all studied patients, suggesting this polymorphism is highly rare in the studied population.CONCLUSION No correlation is detected between studied polymorphisms and patients' response to anti-TNF treatment. Polymorphism rs113054794 is not detected in our population.
文摘Objective: To evaluate the effect of anti-TNF therapy on resistance to insulin in patients with rheumatoid arthritis (RA) compared with patients with RA being treated with non-biological DMARDs. Methods: Inactive patients diagnosed with RA (ACR 1987 criteria) (DAS 28 2.6) were included, being treated with anti-tumor necrosis factor inhibitors (anti-TNF) (cases) and non-biological disease-modifying anti-rheumatic drugs (DMARD) (controls), without risk factors for insulin resistance (administration of steroids, body mass index > 25 kg/m2, diabetes mellitus or use of glucose lowering agents, systemic arterial hypertension or use of anti-hypertensive drugs, triglycerides > 150 mg/dl, hypercholesterolemia > 200 mg/dl, high-density lipoproteins 40 mg/dl in men and 50 mg/in women, or with lipids lowering agents, waist measurement > 88 cm in women and > 102 cm in men). We used HOMA (Homeostasis Model Assessment) to determine insulin resistance in both groups, HOMA being defined as >1 and sensitivity to insulin using QUICKI (Insulin Sensitivity Check Index), ≥0.38 being considered as normal. The Mann Whitney U was used for the statistical analysis. Results: A total of 28 patients, 15 being treated with non-biological DMARDs and 13 with anti-TNF therapy, were evaluated;89.7%, of which were women. Average age: 43.5 (range 21 - 62);the average HOMA index of the non-biological DMARD group was 1.58 (range 0.7 - 5.4), compared with patients treated with anti-TNF therapy, 1.18 (range 0.2 - 4.3) (P = 0.5). The average QUICKI index was 0.36 (range 0.30 - 0.42) in patients treated with non-biological DMARD, compared with0.37 inpatients treated with anti-TNF therapy (range 0.30 - 0.51) (P = 0.8). Conclusion: Resistance to insulin manifested itself in both groups, although there was a greater trend of less insulin resistance and greater sensitivity in the anti-TNF group;this was probably not statistically significant due to the sample size.
文摘Summary： The anti-tumor effect and mechanism of SEA-Fab＇ coupled protein on gastric tumor was studied. The target cell Walke-256 was treated with SEA-Fab＇ synthesized chemically or SEA respectively for 24 h, 36 h or 72 h. PBMC＋Walke-256 cells served as controls. The apoptotic index of SEA-Fab＇ against effector cells was detected. In the mouse gastric cancer models （n=60）, SEA-Fab＇, SEA and normal saline was injected in experimental group, SEA group and control group respectively. The occurrence and weight of tumor was observed. The results showed that the apoptotic index was significantly higher in the SEA-Fab＇ （34.6 -68.9%） and SEA group （15.5-31.9%） than in PBMC＋Walker-256 group （5.5%-12.8%） with the difference being significant （P〈0.01）. And there was significant difference between SEA-Fab＇ group and SEA group （P〈0.01）. The tumor weight in SEA-Fab＇, SEA and control groups was 3.6±0.53 g, 0. 78±0. 26 g and 0.49±0. 17 g respectively with the difference being statistically significant between the SEA-Fab＇ group, SEA group and the control group （P〈0.01）. In the SEA-Fab＇s and SEA groups, there were CD4^＋ T and CD8^＋ T cell infiltrates, but in the cotnrol group, no or few T lymphocytes were seen in the mouse tumor tissue. It was concluded that SEA-Fab＇ was more effective to activate T lymphocytes to kill the tumor cells than SEA used alone. It was feasibility by using the monoclonal antibody as carrier to perform the targeted Immunotherapy of gatric tumor.
文摘In 1974, in Nature, one of us has proposed a radically new idea that led to the development of anticytokine therapy which is now used around the world for the treatment of autoimmune diseases. We were the first to use antibodies to IFN-γ and were some of the first to suggest using antagonists of TNF-α in the treatment of autoimmune and inflammatory diseases as well. Our method suppresses one of the main pathogenetic mechanisms of these diseases. Antibodies to IFN-γ and TNF-α exhibit dramatic effects on clinical manifestations of rheumatoid arthritis (RA). However, in our trial ultrasound assessment of the synovial membrane thickness in RA patients showed that only anti-IFN-γ exerted pronounced anti-inflammatory effect. Some patients who underwent treatment with antibodies to TNF-α developed a number of complications. Anticytokine therapy (mono- and poly-) alone or in combination with other drugs can possibly be used not only in the treatment of autoimmune diseases, but also in other pathologies with cytokine synthesis disturbances (a number of neurological, psychiatric, endocrine, and other diseases).
文摘The increase risk of cancer development in patients with inflammatory intestinal disease (IBD) has already studied for decades. The anti-TNF therapy has changed the treatment strategy of IBD. By using on a larger scale and for a longer time, the anti-TNF raised concern over its potential adverse events. A male Crohn’s disease (CD) patient, 55 years old, diagnosed for nine years, treated with infliximab for 6 years. In 2011, he underwent a nupper endoscopy (UE) which showed flat erosive gastritis with moderate intensity in antrum, gastric polyps and gastric erosion. Pathological examination revealed a chronic gastritis in erosive activity and search for Helicobacter pylori resulted positive. In May 2014, the patient was asymptomatic, when it held UE, which showed suggestive lesion of early gastric cancer, measuring 1.5 cm and search for Helicobacter pylori negative. Histopathological exams confirmed the adenocarcinoma. The patient underwent to a laparoscopic surgery (total gastrectomy with lymphadenectomy and reconstruction Roux-en-Y). Risk factors for the development of gastric cancer in general population are already well defined. However studying a possible association among CD and the different therapeutic modalities used in the treatment of this disease with gastric cancer appearance is important to set specific assessment strategies, prevention and follow-up. While there is no consensus on a proper monitoring for gastric cancer prevention in these patients, individualized conduct, taking into account individual characteristics, family record and other risk factors, should be adopted to avoid unfavorable outcomes in CD patients.
